A Two-dose Primary Vaccination Study of a Tetravalent Dengue Virus Purified Inactivated Vaccine vs. Placebo in Healthy Adults

A Phase I, Randomized, Placebo-Controlled, Observer-blind, Two-dose (0-28 Day Schedule) Primary Vaccination Study of Walter Reed Army Institute of Research (WRAIR) Tetravalent Dengue Virus Purified Inactivated Vaccine (TDENV-PIV) in Healthy Adults in a Non-Endemic Region

The study is designed to afford a safety and immunogenicity assessment of three Tetravalent Dengue Virus-Purified Inactivated Vaccine(TDENV-PIV) vaccine candidates.

The study is designed to afford a safety and immunogenicity assessment of three Tetravalent Dengue Virus-Purified Inactivated Vaccine(TDENV-PIV) vaccine candidates, each formulated with a different adjuvant: either aluminum hydroxide, AS01E or AS03B (adjuvants used in Glaxo Smith Kline (GSK) Biologicals' hepatitis B candidate vaccine, malaria candidate vaccine and pandemic flu vaccine, respectively). Each vaccine candidate will contain 1 µg of purified virus antigen per each of the four DENV types. Additionally, the study will evaluate an alum adjuvanted TDENV-PIV vaccine candidate containing 4 µg of purified virus antigen per each of the four DENV types. The control group will receive a saline placebo. All experimental vaccinations will be administered according to a 2-dose schedule, 28 days apart.

Inclusion Criteria:

• Subjects who the investigator believes can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits, etc.)

• A male or female between 18 and 39 years of age (inclusive) at the time of consent

• Written informed consent obtained from the subject

• Healthy subjects as established by medical history and clinical examination before entering into the study

• Female subjects of non-childbearing potential (non-childbearing potential is defined as having either a current tubal ligation at least three months prior to enrollment, hysterectomy, ovariectomy, or is post-menopause). See Definition of Terms for adequate contraception.

• Female subjects of childbearing potential may be enrolled in the study, if the subject has:

  • Practiced adequate contraception for 30 days prior to vaccination, and
  • A negative urine pregnancy test on the day of vaccination, and
  • Agreed to continue adequate contraception until two months after completion of the vaccination series

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines/placebo during the period starting 30 days preceding the first dose of study vaccine/placebo and/or planned use during the study period

• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 180 days prior to the first vaccine/placebo dose (for corticosteroids, this will mean prednisone ≥ 20 mg/day or equivalent; inhaled and topical steroids are allowed)

• Planned administration or administration of a vaccine/product not foreseen by the study protocol during the period starting 30 days prior to the first dose of vaccine/placebo until after the visit at Day 56 (if influenza activity warrants vaccination of healthy young adults, influenza vaccination will be encouraged and will not lead to study exclusion)

• Planned administration of any flavivirus vaccine for the entire study duration

• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).

• Family history of congenital or hereditary immunodeficiency

• History of, or current auto-immune disease

• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine/placebo or related to a study procedure

• Major congenital defects or serious chronic illness

• History of any neurological disorders or seizures

• Acute disease and/or fever (≥37.5°C/99.5°F oral body temperature) at the time of enrollment (a subject with a minor illness, i.e., mild diarrhea, mild upper respiratory infection, etc., without fever, may be enrolled at the discretion of the investigator)

• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality,as determined by physical examination or laboratory screening tests

• Administration of immunoglobulins and/or any blood products during the period starting 90 days preceding the first dose of study vaccine/placebo or planned administration during the study period

• History of chronic alcohol consumption and/or drug abuse

• Pregnant or lactating female or female planning to become pregnant or planning to discontinue contraceptive precautions

• A planned move to a location that will prohibit participating in the trial until study end for the participant

• Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study.

• Subject seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV)

• Safety laboratory test results that are outside the acceptable values at screening. The following values are not acceptable:

  • >110% upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, creatinine, serum urea nitrogen (SUN) and bilirubin (total and direct)
  • <100% lower limit of normal (LLN) or > 120% ULN for hemoglobin, hematocrit and platelet count
  • <75% LLN or >110% ULN for total white blood cell count (WBC) Note that all screening laboratory results must be either within normal limits (WNL) or no more than Grade l not clinically significant (NCS)

(LLN=lower limit of normal; ULN= upper limit of normal, WNL= within normal limits, NCS= not clinically significant)